Regulation and molecular mechanism of adiponectin on the proliferation, apoptosis, autophagy, and chemosensitivity of LN18 Glioma cell line.

This study aimed to explore the regulatory effects and associated mechanisms of adiponectin on apoptosis and proliferation in the LN18 glioma cell line through the AMPK and Akt signaling pathways. Additionally, we sought to elucidate the impact of adiponectin on the chemosensitivity of the LN18 glioma cell line to temozolomide (TMZ). The proliferation rate of glioma cells treated with adiponectin was assessed using the cholecystokinin (CCK8) assay. The Western blot analysis was employed to assess the expression of p-Akt, p-AMPK, p-mTOR, cleaved caspase3, Bax, Cyclin D1, and Cyclin B1 following adiponectin treatment. Cell apoptosis was quantified using AnnexinV/PI flow cytometry, while changes in the cell cycle were detected using PI staining flow cytometry. The findings revealed that adiponectin upregulates p-AMPK expression and downregulates p-mTOR expression in the PTEN wild-type glioma cell line LN18, with no discernible effect on p-Akt expression. Moreover, adiponectin inhibits the proliferation rate of the PTEN wild-type glioma cell line LN18, enhances the expression of cleaved caspase3 and Bax, and significantly elevates the apoptosis rate, as evidenced by AnnexinV/PI flow cytometry. Adiponectin was observed to suppress the expression of Cyclin D1 and Cyclin B1, increase the number of cells in the G1 phase, and promote autophagy. Additionally, adiponectin augments the expression of Beclin1 and the ratio of LC3II/I in the PTEN wild-type glioma cell line LN18, while decreasing p62 expression. In conclusion, this study posits that adiponectin holds therapeutic promise for glioma treatment. Furthermore, adiponectin enhances the inhibitory effect of TMZ on the proliferation rate of LN18 cells when treated with 0.1 mM and 1 mM TMZ. These results collectively suggest that adiponectin impedes proliferation, encourages apoptosis and autophagy in the LN18 glioma cell line, and heightens its sensitivity to the chemotherapeutic drug TMZ.

Post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia: a case report.

BACKGROUND: Pneumocephalus is rare in vaginal deliveries. Pneumocephalus may be asymptomatic or present with signs of increased intracranial pressure. However, parturients who received epidural anesthesia with air in their brains may experience low intracranial pressure headaches after giving birth, causing the diagnosis of pneumocephalus to be delayed. We report a case of a parturient who developed post-dural puncture headache combined with pneumocephalus secondary to vaginal delivery following epidural anesthesia. CASE PRESENTATION: A 24-year-old G1P0 Chinese woman at 38 weeks gestation was in labor and received epidural anesthesia using the loss of resistance to air technique and had a negative prior medical history. She presented with postural headache, neck stiffness and auditory changes 2 h after vaginal delivery. The head non-contrast computed tomography revealed distributed gas density shadows in the brain, indicating pneumocephalus. Her headache was relieved by bed rest, rehydration, analgesia, and oxygen therapy and completely disappeared after 2 weeks of postpartum bed rest. CONCLUSIONS: This is the first report that positional headaches after epidural anesthesia may not indicate low intracranial pressure alone; it may combine with pneumocephalus, particularly when using the loss of resistance to air technique. At this moment, head computed tomography is essential to discover other conditions like pneumocephalus.

Loganin attenuates neuroinflammation after ischemic stroke and fracture by regulating α7nAChR-mediated microglial polarization.

Fracture in acute stage of ischemic stroke can increase inflammatory response and enhance stroke injury. Loganin alleviates the symptoms of many inflammatory diseases through its anti-inflammatory effect, but its role in ischemic stroke and fracture remains to be explored. Here, mice were handled with permanent middle cerebral artery occlusion (pMCAO) followed by tibial fracture 1 day later to establish a pMCAO+fracture model. Loganin or Methyllycaconitine (MLA, a specific a7nAchR inhibitor) were intragastrically administered 2 or 0.5 h before pMCAO, respectively. And mouse motor function and infarct volume were evaluated 3 days after pMCAO. We found that loganin alleviated the neurological deficit, cerebral infarction volume, and neuronal apoptosis (NeuN+ TUNEL+ ) in mice with pMCAO+fracture. And loganin suppressed pMCAO+fracture-induced neuroinflammation by promoting M2 microglia polarization (Iba1+ CD206+ ) and inhibiting M1 microglia polarization (Iba1+ CD11b+ ). While administration with MLA reversed the protective effect of loganin on pMCAO+fracture-induced neurological deficit and neuroinflammation. Next, LPS was used to stimulate BV2 microglia to simulate pMCAO+fracture-induced inflammatory microenvironment in vitro. Loganin facilitated the transformation of LPS-stimulated BV2 cells from M1 pro-inflammatory state (CD11b+ ) to M2 anti-inflammatory state (CD206+ ), which was antagonized by treatment with MLA. And loganin induced autophagy activation in LPS-stimulated BV2 cells by activating a7nAchR. Moreover, treatment with rapamycin (an autophagy activator) neutralized the inhibitory effect of MLA on loganin induced transformation of BV2 cells to M2 phenotype. Furthermore, BV2 cells were treated with LPS, LPS + loganin, LPS + loganin+MLA, or LPS + loganin+MLA+ rapamycin to obtain conditioned medium (CM) for stimulating primary neurons. Loganin reduced the damage of primary neurons caused by LPS-stimulated BV2 microglia through activating a7nAchR and inducing autophagy activation. In conclusion, loganin played anti-inflammatory and neuroprotective roles in pMCAO + fracture mice by activating a7nAchR, enhancing autophagy and promoting M2 polarization of microglia.

A tool for predicting overall survival in patients with Ewing sarcoma: a multicenter retrospective study.

OBJECTIVE: The aim of this study was to establish and validate a clinical prediction model for assessing the risk of metastasis and patient survival in Ewing's sarcoma (ES). METHODS: Patients diagnosed with ES from the Surveillance, Epidemiology and End Results (SEER) database for the period 2010-2016 were extracted, and the data after exclusion of vacant terms was used as the training set (n=767). Prediction models predicting patients' overall survival (OS) at 1 and 3 years were created by cox regression analysis and visualized using Nomogram and web calculator. Multicenter data from four medical institutions were used as the validation set (n=51), and the model consistency was verified using calibration plots, and receiver operating characteristic (ROC) verified the predictive ability of the model. Finally, a clinical decision curve was used to demonstrate the clinical utility of the model. RESULTS: The results of multivariate cox regression showed that age, , bone metastasis, tumor size, and chemotherapy were independent prognostic factors of ES patients. Internal and external validation results: calibration plots showed that the model had a good agreement for patient survival at 1 and 3 years; ROC showed that it possessed a good predictive ability and clinical decision curve proved that it possessed good clinical utility. CONCLUSIONS: The tool built in this paper to predict 1- and 3-year survival in ES patients ( https://drwenleli0910.shinyapps.io/EwingApp/ ) has a good identification and predictive power.

Protocol of End-PSCI trial: a multicenter, randomized controlled trial to evaluate the effects of DL-3-n-butylphthalide on delayed-onset post stroke cognitive impairment.

BACKGROUND: Delayed-onset post stroke cognitive impairment (PSCI) results from secondary neurodegeneration induced by stroke. Whereas targeted prevention or treatment strategies are still missing due to lack of evidences. This trial aims to evaluate the preventive effects of DL-3-n-butylphthalide (NBP) on delayed-onset PSCI. METHODS: Effects of NBP on Delayed-onset Post Stroke Cognitive Impairment (End-PSCI) is a prospective, parallel-group, open-label, multicenter, randomized controlled trial with blinded outcome assessment. Hospital patients with acute cerebral infarction (within 2 weeks of onset) will be randomized into either standard medical therapy group or standard medical therapy combined NBP treatment group (NBP 200 mg, three times per day for 24 weeks). The primary outcome is the difference of incidence of delayed-onset PSCI between two groups. The secondary outcomes include difference of white matter degeneration, cognitive scores and prevalence of early-onset PSCI between two groups. DISCUSSION: End-PSCI trial will provide evidences for NBP preventing delayed-onset PSCI. The secondary outcomes will also provide valuable insights into the pathogenesis of delayed-onset PSCI and mechanism of NBP's actions. TRIAL REGISTRATION: Trialsearch.who.int , ChiCTR2000032555, 2020/5/2, prospectively registered.

Sleep disturbance is associated with mild cognitive impairment: a community population-based cross-sectional study.

BACKGROUND: Sleep is conducive to the elimination of brain metabolites and the recovery of brain function. However, the relationship between sleep disturbance and Mild Cognitive Impairment is not fully been determined. METHODS: This was a community population-based cross-sectional study. A total of 1,443 participants from a village in the suburbs of Xi'an, China were enrolled in 2017. Sleep quality was evaluated using the Pittsburgh sleep quality index (PSQI), and sleep disturbance was defined as a PSQI score > 5. Mini-Mental State Examination (MMSE) was used to assess cognitive function and Mild Cognitive Impairment(MCI) was defined as the MMSE score less than cutoff values and meets the diagnostic criteria. Univariate and multivariate analyses were used to analyze the relationships between sleep disturbance and MCI. RESULTS: Among 1,443 subjects, 69(4.78%) had MCI, and 830 (57.52%) had sleep disturbance. In bivariate analysis, MCI was associated with sleep disturbance (ρ = 0.094, P<0.001). In the binary logistic regression, MCI was positively associated with the sleep disturbance (OR = 2.027, 95%CI = 1.112-3.698, P = 0.021). In the internal constitution of PSQI, MCI was negatively associated with the habitual sleep efficiency (OR = 0.447, 95%CI = 0.299-0.669, P < 0.001). Compared with waking up before or at 7 am, waking up after 7 am (OR = 0.555, 95%CI = 0.309-0.995, P = 0.048), or 8 am (OR = 0.296, 95%CI = 0.097-0.902, P = 0.032) was probably more likely to have normal cognition. However, people who slept more than 8 h a day might be more likely to suffer from MCI (OR = 5.560, 95%CI = 1.419-21.789, P = 0.014). CONCLUSION: Sleep disturbance is associated with Mild Cognitive Impairment. However, the causal relationship between them is not clear. It needs to be further studied.

Apolipoprotein E ε4 Allele is Associated With Plasma Amyloid Beta and Amyloid Beta Transporter Levels: A Cross-sectional Study in a Rural Area of Xi'an, China.

OBJECTIVE: The effects of the Apolipoprotein E (ApoE) genotype on peripheral amyloid beta (Aß) and Aß transporter levels are still unclear. Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) are the major transporter for Aß, which can prevent plasma Aß from flowing into brain. The aim of this study was to investigate the relationships between the ApoE genotype and plasma Aß, sLRP1, sRAGE levels. DESIGN: Cross-sectional study. SETTING: The committee office of the village. PARTICIPANTS: Residents lived in the village for more than 3 years, aged 40-85 years (n = 1,119, 63.5% women). MEASUREMENTS: Plasma biomarkers include ApoE genotype, Aß, sLRP1, sRAGE, fasting blood-glucose, and blood lipids. General information, medical history, living habits, and cognitive status (cognitive impairment or not) were also collected. RESULTS: After controlling for all possible covariates, multiple linear regression analysis showed that the plasma level of Aß42 was higher and log-transformed sLRP1 was lower in ApoE ε4 carriers than that in noncarriers (ßAß42 = 1.214, 95% confidence interval: 0.105-2.316, pAß42 = 0.031; ßsLRP1 = -0.075, 95% confidence interval: -0.129 to -0.021, psLRP1 = 0.006, respectively). Partial correlation analysis showed that plasma Aß40 was positively correlated with log-transformed sLRP1 and log-transformed sRAGE (rsLRP1 = 0.116, psLRP1 <0.001; rsRAGE = 0.078, psLRP1 = 0.009, respectively). Plasma Aß42 was positively correlated with log-transformed sRAGE (r = 0.072, p = 0.017). CONCLUSION: ApoE ε4 carriers had higher plasma Aß42 levels and lower sLRP1 levels. These data indicated that the ApoE ε4 allele may also contribute to the pathogenesis of Alzheimer's disease through its effects on peripheral Aß42 and sLRP1 levels, but it needs to be further elucidated.

The relationship between blood lipids and plasma amyloid beta is depend on blood pressure: a population-based cross-sectional study.

BACKGROUND: It is believed that deposition of amyloid beta (Aß) in the brain is the central pathological changes of Alzheimer's disease (AD), which triggers a series of pathological processes. However, the relationship between dyslipidemia and AD is uncertain. Considering the peripheral Aß levels are related to brain Aß deposition, we explore the relationships between blood lipids and plasma Aß. METHODS: Participants who lived in the selected village of Xi'an for more than 3 years were enrolled, aged 40-85 years (n = 1282, 37.9% male). Fasting blood lipid, plasma Aß levels, basic information and living habits were measured. Multiple linear regressions were used. RESULTS: In total population, blood lipids were not associated with plasma Aß. After stratified by blood pressure, serum total cholesterol (TC) and low-density lipoprotein (LDL-c) were positively associated with plasma Aß42 levels (ßTC = 0.666, PTC = 0.024; ßLDL-c = 0.743, PLDL-c = 0.011, respectively) in normal blood pressure. LDL-c was negatively associated with plasma Aß40 levels (ß = - 0.986, P = 0.037) in high blood pressure. CONCLUSION: Elevated plasma Aß42 levels are associated with higher TC and LDL-c in normal blood pressure. Elevated plasma Aß40 levels are associated with lower LDL-c in high blood pressure. This indicated that the relationships between blood lipids and plasma Aß were confounded by blood pressure.

Bone Fracture Enhanced Blood-Brain Barrier Breakdown in the Hippocampus and White Matter Damage of Stroke Mice.

BACKGROUND: Tibia fracture (BF) before stroke shortly causes long-term post-stroke memory dysfunction in mice. The mechanism is unclear. We hypothesize that BF enhances neuroinflammation and blood brain barrier (BBB) breakdown in the hippocampus and white matter (WM) damage. METHODS: Mice were assigned to groups: BF, stroke, BF+stroke (BF 6 h before stroke) and sham. BBB integrity was analyzed 3 days after the surgeries and WM injury was analyzed 3 days and 8 weeks after the surgeries. RESULTS: Stroke and BF+stroke groups had more activated microglia/macrophages and lower levels of claudin-5 in the ipsilateral hippocampi than the BF group. BF+stroke group had the highest number microglia/macrophages and the lowest level of claudin-5 among all groups and had fewer pericytes than BF group. Stroke and BF+stroke groups had smaller WM areas in the ipsilateral basal ganglia than the sham group 8 weeks after the injuries. The BF+stroke group also had smaller WM areas in the ipsilateral than sham and BF groups 3 days after the injuries and in the contralateral basal ganglia than stroke and BF groups 8 weeks after the injuries. CONCLUSIONS: BF exacerbates neuroinflammation and BBB leakage in the hippocampus and WM damage in basal ganglia, which could contribute to the long-lasting memory dysfunction in BF+stroke mice.

Chronic Sleep Restriction Induces Aß Accumulation by Disrupting the Balance of Aß Production and Clearance in Rats.

Amyloid-ß (Aß) plays an important role in Alzheimer's disease (AD) pathogenesis, and growing evidence has shown that poor sleep quality is one of the risk factors for AD, but the mechanisms of sleep deprivation leading to AD have still not been fully demonstrated. In the present study, we used wild-type (WT) rats to determine the effects of chronic sleep restriction (CSR) on Aß accumulation. We found that CSR-21d rats had learning and memory functional decline in the Morris water maze (MWM) test. Meanwhile, Aß42 deposition in the hippocampus and the prefrontal cortex was high after a 21-day sleep restriction. Moreover, compared with the control rats, CSR rats had increased expression of ß-site APP-cleaving enzyme 1 (BACE1) and sAPPß and decreased sAPPα levels in both the hippocampus and the prefrontal cortex, and the BACE1 level was positively correlated with the Aß42 level. Additionally, in CSR-21d rats, low-density lipoprotein receptor-related protein 1 (LRP-1) levels were low, while receptor of advanced glycation end products (RAGE) levels were high in the hippocampus and the prefrontal cortex, and these transporters were significantly correlated with Aß42 levels. In addition, CSR-21d rats had decreased plasma Aß42 levels and soluble LRP1 (sLRP1) levels compared with the control rats. Altogether, this study demonstrated that 21 days of CSR could lead to brain Aß accumulation in WT rats. The underlying mechanisms may be related to increased Aß production via upregulation of the BACE1 pathway and disrupted Aß clearance affecting brain and peripheral Aß transport.

Optimizing early enteral nutrition in severe stroke (OPENS): protocol for a multicentre randomized controlled trial.

BACKGROUND: Malnutrition is one of the crucial factors associated with poor prognosis in critical ill patients, yet a significant evidence gap surrounds the management of initial enteral feeding in severe stroke. The Optimizing Early Enteral Nutrition in Severe Stroke (OPENS) trial will compare a strategy of modified full enteral nutrition (EN) (standard full EN in conjunction with prokinetic drug) and a strategy of permissive underfeeding (40 to 60% of estimated caloric requirements) with standard full EN (advancement to target nutrition goals) in patients with severe stroke. METHODS: The OPENS trial is a multicenter randomized controlled study. A total of 600 adult patients with severe stroke will be enrolled in 12 study sites in China, and randomized to standard full EN, modified full EN, or permissive underfeeding. The primary outcome measurement is the proportion of participants with a poor outcome (modified Rankin Scale ≥3) at day 90 of enrollment. Secondary outcomes include incidence rates of complications during hospitalization, disability at hospital discharge, and the ability of activities of daily living at day 90 of enrollment. The relationship between intervention and the primary outcome will be analyzed using multivariate logistic regression adjusted for study site, demographics, and baseline characteristics. DISCUSSION: The OPENS trial will explore the optimum initial feeding strategy for acute severe stroke. This trial is, therefore, an important step in bridging the evidence gap surrounding the enteral feeding for patients with severe stroke during the first week of hospitalization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02982668 ; First Posted: December 5, 2016.

The gender- and age- dependent relationships between serum lipids and cognitive impairment: a cross-sectional study in a rural area of Xi'an, China.

BACKGROUND: Serum lipids [total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG)] are risk factors for stroke, but the relationships between serum lipids and cognitive impairment have not been verified completely. In this study, we studied the relationships between serum lipids and cognitive impairment and explored whether gender and age had effects on the relationships. METHODS: In this cross-sectional study, we collected serum lipids and cognitive function information from 1762 participants (aged 40-85). Univariate analysis, multivariate analysis, and both gender- and age-based stratified multivariate analysis were used. RESULTS: In the entire sample set, there was no significant correlation between serum lipid parameters (TC, LDL-C, HDL-C and TG) and cognitive impairment. In both gender- and age-based stratified multivariate analysis, high serum TC was positively associated with cognitive impairment in the elderly (> 55) male participants (OR = 4.404, 95% CI = 1.264-15.344, p = 0.02), and high serum LDL-C was positively correlated with cognitive impairment in the elderly female subjects (OR = 2.496, 95% CI = 1.057-5.896, p = 0.037), while high serum TG was negatively associated with cognitive impairment in the middle-aged (≤ 55) male participants (OR = 0.157, 95% CI = 0.051-0.484, p = 0.001). CONCLUSIONS: The relationships between serum lipids and cognitive impairment are gender- and age- dependent, with high serum TC and LDL-C may be risk factors of cognitive impairment in the elderly male and female subjects respectively, while high serum TG may be protector of cognitive impairment in the middle-aged male participants.

Association of white matter hyperintensities with migraine features and prognosis.

BACKGROUND: White matter hyperintensities (WMHs) are frequently detected in migraine patients. However, their significance and correlation to migraine disease burden remain unclear. This study aims to examine the correlation of WMHs with migraine features and explore the relationship between WMHs and migraine prognosis. METHODS: A total of 69 migraineurs underwent MRI scans to evaluate WMHs. Migraine features were compared between patients with and without WMHs. After an average follow-up period of 3 years, these patients were divided into two groups, according to the reduction of headache frequency: improved and non-improved groups. The percentage and degree of WMHs were compared between these two groups. RESULTS: A total of 24 patients (34.8%) had WMHs. Patients with WMHs were significantly older (39.0 ± 7.9 vs. 30.6 ± 10.4 years, P < 0.001) and had a longer disease duration (median: 180.0 vs. 84.0 months, P = 0.013). Furthermore, 33 patients completed the follow up period (15 patients improved and 18 patients did not improve). Patients in the non-improved group had a higher frequency of WMHs (55.6% vs. 13.3%, P = 0.027) and median WMHs score (1.0 vs. 0.0, P = 0.030). CONCLUSIONS: WMHs can predict unfavorable migraine prognosis. Furthermore, WMHs may have a closer association with age than migraine features.

Right-to-left shunt may be prone to affect the white matter integrity of posterior circulation in migraine without aura.

Numerous studies have indicated an association between migraine and right-to-left shunt. However, little is known about whether right-to-left shunt has an effect on the migraine brain. This observational study aims to explore the impact of right-to-left shunt on the brain of migraine without aura on microstructural level. Thirty-five patients with migraine without aura were enrolled in this study. Contrast-enhanced Transcranial Doppler was performed to evaluate the status of right-to-left shunt. Three-dimensional T1-weighted and diffusion tensor images were acquired for data analysis. We employed voxel-based morphometry and tract-based spatial statistical analyses to assess the differences of gray and white matter between migraineurs with and without right-to-left shunt, respectively. Among the 35 patients, 19 (54.3%) patients had right-to-left shunt. There were no significant differences in headache features between migraineurs with and without right-to-left shunt. There were significant increases of mean and radial diffusivity in migraineurs with right-to-left shunt compared with migraineurs without right-to-left shunt. The alterations were primarily located in the right posterior thalamic radiation, secondly in the body of corpus callosum and the right superior corona radiata. No significant differences were observed in values of fractional anisotropy and axial diffusivity. No significant between-group differences were found in gray matter volume. Right-to-left shunt may cause alterations of white matter integrity in migraine without aura, and the alterations are more likely to be located at the posterior circulation.

Impact of Bone Fracture on Ischemic Stroke Recovery.

Stroke is one of the most devastating complications of bone fracture, occurring in up to 4% of patients after surgical repair for hip fracture. Bone fracture and ischemic stroke have many common risk factors. The impact of bone fracture on stroke recovery has not drawn much attention in the research field. Bone fracture could occur in stroke patients at different times during the recovery phase, which steepens the trajectory of cognitive decline, greatly affects the quality of life, and causes a heavy burden on healthcare resources. In this paper, we reviewed the growing information on the pathophysiological mechanisms by which bone fracture may affect ischemic stroke recovery process.

The Design and Rationale of a Clinical Trial Evaluating Limb Postconditioning in Young Patients with Intracranial Arterial Stenosis.

OBJECTIVES: To examine the effectiveness of bilateral arm remote ischemic postconditioning (RIPC) on the rehabilitation of nerve function and collateral circulation in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). SETTING: Open, controlled, prospective trial (EPIC-sICAS trial) in Xi'an, Shaanxi, China. PARTICIPANTS: Up to 100 sICAS patients (age: 18-45 years, gender balance) who fulfill the inclusion and exclusion criteria will be enrolled and randomized to intervention group and control group (n ~ 50/group). INTERVENTIONS: The intervention group will undergo ischemia and reperfusion on both arms twice a day for 6 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Mean changes in collateral circulation from baseline to the end of the 6-month RIPC treatment period, measured by dynamic contrast-enhanced magnetic resonance imaging, will be the primary outcome. Clinical symptoms, serum levels of vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) will be compared as secondary outcome. RESULTS: A safety evaluation and preliminary experiment of the EPIC-sICAS trial were completed in November 2014 and March 2015, respectively. Overall and regional brain hemodynamics remained stable throughout RIPC. Activities of daily living score and serum VEGF and bFGF levels were significantly higher (P < .05) in the intervention group. CONCLUSIONS: Repetitive bilateral arm RIPC appears to have protective effects in the brain related to angiogenesis promotion and neuroprotection in the acute phase of sICAS. Assessment of the role of RIPC in collateral circulation requires imaging tests and longer follow-up, as planned in the EPIC-sICAS trial.

Variance of Serum Lipid Levels in Stroke Subtypes.

BACKGROUND: An increasing number of epidemiological studies have identified a close relationship between dyslipidemia and atherosclerotic stroke. Indeed, lipid metabolism is significantly different among the different ischemic stroke subtypes. There are few studies available regarding risk factors for specific subtypes of ischemic stroke, and in particular, there is little evidence about the role of dyslipidemia. The aim of this study is to determine the relationship between acute ischemic stroke subtype and serum lipid level. METHODS: The levels of serum lipid including TC, TG, LDL-C, HDL-C, apoA, apoB, apoE, and LP (a) were tested in 362 ischemic stroke patients and 181 healthy controls. Lipid levels were analyzed in stroke subtypes according to the TOAST classification. RESULTS: Levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP (a) were significantly higher and HDL-C levels were significantly lower in the patient group relative to control. The TC/HDL-C ratio, TG/HDL-C ratio, and LDL-C/HDL-C ratio were remarkably higher in the patient group. The levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP(a) were markedly higher and HDL-C was markedly lower in the large-artery atherosclerosis stroke subtype relative to the cardioembolism subtype. Compared with the small-vessel occlusion group, the level of LP(a), TC, and TC/HDL-C were strikingly higher in the cardioembolism group. The TC/HDL-C ratio was different among subgroups, with the large-artery atherosclerosis group exhibiting the highest value. For TC, TG, LDL-C, apoA, apoB, apoE, LP(a), TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C levels a statistically significant difference was found between the large-artery atherosclerosis group and the small-vessel occlusion group. CONCLUSIONS: We found that LDL-C and TC levels may be independent predictors for the occurrence of large-artery atherosclerotic stroke.

Enlarged perivascular spaces predict malignant cerebral edema after acute large hemispheric infarction.

INTRODUCTION: Enlarged perivascular spaces (EPVS) are considered early manifestations of impaired clearance mechanisms in the brain; however, it is unclear whether EPVS they are associated with the development of malignant cerebral edema (MCE) after large hemispheric infarction (LHI). Therefore, we investigated the predictive value of EPVS in predicting MCE in LHI. METHODS: Patients suffering from acute LHI were consecutively enrolled. EPVS were rated after the stroke with validated rating scales from magnetic resonance imagess. Patients were divided into two groups according to the occurrence of MCE. Logistic regression was used to analyze the relationship between EPVS and MCE in the basal ganglia (BG) and centrum semiovale (CS) regions. Receiver operating characteristic (ROC) curves assessed the ability of EPVS individually and with other factors in predicting MCE. RESULTS: We included a total of 255 patients, of whom 98 were MCE patients (58 [59.2%] males, aged 70 [range=61.75-78] years) and found that atrial fibrillation, National Institutes of Health Stroke Scale score, infarct volume, neutrophil-lymphocyte ratio, and moderate-to-severe CS-EPVS were positively associated with MCE. After adjusting for confounds, moderate-to-severe CS-EPVS remained independent risk factor of MCE (odds ratio=16.212, p＜0.001). According to the ROC analysis, MCE was highly suspected when CS-EPVS > 14 (sensitivity=0.82, specificity=0.48), and the guiding value were higher when CS-EPVS combined with other MCE predictors (area under the curve=0.90, sensitivity=0.74, specificity=0.90). CONCLUSION: CS-EPVS were important risk factor for MEC in patients with acute LHI and can help identify patients at risk for MCE.

Trends on Prevalence, All-Cause Mortality, and Survival Status of Dementia Patients in Rural China Based on Pooling Analysis.

Objectives: No study has reported secular trends in dementia prevalence, all-cause mortality, and survival status in rural China. Methods: We established two cohorts (XRRCC1 and XRRCC2) in the same region of China, 17 years apart, to compare dementia prevalence, all-cause mortality, and survival status, and performed regression analysis to identify associated factors. Results: Dementia prevalence was 3.49% in XRRCC1 and 4.25% in XRRCC2, with XRRCC2 showing a significantly higher prevalence (OR = 1.79, 95%CI: 1.2-2.65). All-cause mortality rates for dementia patients were 62.0% in XRRCC1 and 35.7% in XRRCC2. Mortality in the normal population of XRRCC2 decreased by 66% compared to XRRCC1, mainly due to improved survival rates in women with dementia. Dementia prevalence was positively associated with age >65, spouse-absent status, and stroke, and negatively associated with ≥6 years of education. Conclusion: Dementia prevalence in rural China increased over 17 years, while mortality decreased. Major risk factors include aging, no spouse, and stroke, with higher education offering some protection.

Solasonine ameliorates cerebral ischemia-reperfusion injury via suppressing TLR4/MyD88/NF-κB pathway and activating AMPK/Nrf2/HO-1 pathway.

Solasonine (SS), the main active ingredient of Solanum nigrum L., has been reported to possess a variety of pharmacological properties. A recent study demonstrated a neuroprotective effect of SS in a mouse nerve injury model. However, its protective effects on cerebral ischemia/reperfusion injury (CIRI) remain to be elucidated. We investigated herein the in vitro and in vivo neuroprotective effects of SS. Primary hippocampal neurons were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to construct an in vitro model while rats were treated with middle cerebral artery occlusion/reperfusion (MCAO/R) to establish an in vivo CIRI model. The results showed that SS reduced OGD/R-induced inflammatory responses of neurons by blocking secretion of TNF-α, IL-1ß and IL-6. Moreover, SS ameliorated OGD/R-induced oxidative stress in neurons by decreasing the level of ROS and MDA and increasing the activity of SOD and GPx. We also found that SS protected neurons from OGD/R-induced apoptosis by down-regulating bax and cleaved caspase-3 and up-regulating bcl-2. The in vivo results revealed that SS administration reduced the infarct volume and alleviated the neurological deficit of MCAO/R rats as well as diminished neuronal damages in these rats. Our investigation on the underlying mechanisms indicated that the neuroprotective effect of SS on CIRI may be associated with the TLR4/MyD88/NF-κB and AMPK/Nrf2/HO-1 pathways. Taken together, these findings demonstrate that SS ameliorates CIRI via suppressing TLR4/MyD88/NF-κB pathway and activating AMPK/Nrf2/HO-1 pathway.